Neuropsychiatric Disease and Treatment (Sep 2023)
Oligodendrocyte Progenitor Cell Transplantation Ameliorates Preterm Infant Cerebral White Matter Injury in Rats Model
Abstract
Zhaoyan Wang,1,* Leping Zhang,1,2,* Yinxiang Yang,1 Qian Wang,1 Suqing Qu,1 Xiaohua Wang,1 Zhixu He,2,3 Zuo Luan1 1Laboratory of Pediatrics, The Sixth Medical Center of PLA General Hospital, Beijing, 100048, People’s Republic of China; 2Guizhou Medical University, Guiyang, 550004, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 563100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zuo Luan; Zhixu He, Email [email protected]; [email protected]: Cerebral white matter injury (WMI) is the most common brain injury in preterm infants, leading to motor and developmental deficits often accompanied by cognitive impairment. However, there is no effective treatment. One promising approach for treating preterm WMI is cell replacement therapy, in which lost cells can be replaced by exogenous oligodendrocyte progenitor cells (OPCs).Methods: This study developed a method to differentiate human neural stem cells (hNSCs) into human OPCs (hOPCs). The preterm WMI animal model was established in rats on postnatal day 3, and OLIG2+/NG2+/PDGFRα+/O4+ hOPCs were enriched and transplanted into the corpus callosum on postnatal day 10. Then, histological analysis and electron microscopy were used to detect lesion structure; behavioral assays were performed to detect cognitive function.Results: Transplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histological analysis revealed structural repair of lesioned areas. Re-myelination of the axons in the corpus callosum was confirmed by electron microscopy. The Morris water maze test revealed cognitive function recovery.Conclusion: Our study showed that exogenous hOPCs could differentiate into CC1+ OLS in the brain of WMI rats, improving their cognitive functions.Keywords: preterm infant, cerebral white matter injury, oligodendrocyte progenitor cells, cell replacement therapy, rat model